Image-guided surgical interventions have the potential to improve surgical outcomes by providing improved visualization and differentiation of normal and pathological tissue intraoperatively and in real-time. Pathology, however, exists across a large range of size scales within the human body, ranging from large tumor masses to genetic mutations in single cells. Currently, the majority of the surgical treatments for cancer are performed at the macro tissue scale. In virtually all surgical oncology interventions, the goal is to remove the entire tumor mass and every tumor cell. Therefore, a critical need exists for an image-guided interventional technology that is capable of real-time intraoperative imaging for the complete resection of a tumor mass, for the detection and removal of individual tumor cells that have migrated across tumor margins, and for the detection of cells that have metastasized to regional lymph nodes. Optical coherence tomography (OCT) is an emerging high-resolution real-time biomedical imaging technology capable of intraoperative imaging for tumor detection and intervention. We propose to investigate the use of OCT for performing high-resolution image-guided surgical interventions for the identification and resection of solid tumors, tissue regions suspicious for occult tumor cells, and loco-regional lymph nodes that show evidence of metastatic involvement. We will develop a high-speed surgical microscope-based OCT system with fast digital-signal-processing hardware. This system will allow for the real-time acquisition, processing, and display of OCT image data. A real-time image-tissue registration system will illuminate regions in the open surgical field that correspond to regions highlighted by the operator on the real-time OCT images. Breast cancer remains a formidable diagnostic and surgical challenge. To date, no OCT imaging studies have investigated the use of this diagnostic technique for this disease. We will utilize a well-characterized rat mammary tumor model to demonstrate the capabilities of our techniques by performing OCT image-guided surgical interventions of mammary tumors in an open surgical field and with an integrated tissue-sampling OCT needle biopsy probe. Studies will also be performed to determine if the use of novel OCT contrast agents can improve the identification and complete resection of the tumors. The use of OCT for image- guided surgical interventions has the long-term goal of improving surgical outcomes by enabling complete resection of tumor by visualizing the surgical field with resolutions that approach histopathology.